The yin and yang of mitochondrial Ca2+ signaling in cell physiology and pathology

Abstract

Mitochondria are autonomous and dynamic cellular organelles orchestrating a diverse range of cellular activities. Numerous cell-signaling pathways target these organelles and Ca²⁺ is one of the most significant. Mitochondria are able to rapidly and transiently take up Ca²⁺, thanks to the mitochondrial Ca²⁺ uniporter complex, as well as to extrude it through the Na⁺/Ca²⁺ and H⁺/Ca²⁺ exchangers. The transient accumulation of Ca²⁺ in the mitochondrial matrix impacts on mitochondrial functions and cell pathophysiology. Here we summarize the role of mitochondrial Ca²⁺ signaling in both physiological (yang) and pathological (yin) processes and the methods that can be used to investigate mitochondrial Ca²⁺ homeostasis. As an example of the pivotal role of mitochondria in pathology, we described the state of the art of mitochondrial Ca²⁺ alterations in different pathological conditions, with a special focus on Alzheimer's disease.

Keywords: ATP; Alzheimer’s disease; Autophagy; Calcium signaling; Cell death; Cell metabolism; Chemical biosensors; GECI; MCUC; Mitochondria; Presenilins.